rs9333238

Variant names:

• chr10-15531367-G-A
• rs9333238
• NM_003638.3:c.2881-216C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003638.3(ITGA8):​c.2881-216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 126,050 control chromosomes in the GnomAD database, including 2,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (2763 hom., cov: 30)
• Consequence: ITGA8 NM_003638.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• Publications: 1 publications found

Genes affected

ITGA8 (HGNC:6144): (integrin subunit alpha 8) Integrins are heterodimeric transmembrane receptor proteins that mediate numerous cellular processes including cell adhesion, cytoskeletal rearrangement, and activation of cell signaling pathways. Integrins are composed of alpha and beta subunits. This gene encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1 protein. The encoded protein is a single-pass type 1 membrane protein that contains multiple FG-GAP repeats. This repeat is predicted to fold into a beta propeller structure. This gene regulates the recruitment of mesenchymal cells into epithelial structures, mediates cell-cell interactions, and regulates neurite outgrowth of sensory and motor neurons. The integrin alpha8beta1 protein thus plays an important role in wound-healing and organogenesis. Mutations in this gene have been associated with renal hypodysplasia/aplasia-1 (RHDA1) and with several animal models of chronic kidney disease. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2014]

ITGA8 Gene-Disease associations (from GenCC):

• renal hypodysplasia/aplasia 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• bilateral renal agenesis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-15531367-G-A is Benign according to our data. Variant chr10-15531367-G-A is described in ClinVar as Benign. ClinVar VariationId is 1264028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003638.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA8	NM_003638.3	MANE Select	c.2881-216C>T		intron	N/A	NP_003629.2	P53708
	ITGA8	NM_001291494.2		c.2836-216C>T		intron	N/A	NP_001278423.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA8	ENST00000378076.4	TSL:1 MANE Select	c.2881-216C>T		intron	N/A	ENSP00000367316.3	P53708
	ITGA8	ENST00000882526.1		c.2881-11955C>T		intron	N/A	ENSP00000552585.1
	ITGA8	ENST00000967017.1		c.2836-11955C>T		intron	N/A	ENSP00000637076.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 28271 AN: 125972 Hom.: 2763 Cov.: 30

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 28286 AN: 126050 Hom.: 2763 Cov.: 30 AF XY: 0.227 AC XY: 14016 AN XY: 61722

African (AFR) AF: 0.179 AC: 5978 AN: 33360

American (AMR) AF: 0.227 AC: 3079 AN: 13538

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 642 AN: 2794

East Asian (EAS) AF: 0.143 AC: 738 AN: 5148

South Asian (SAS) AF: 0.167 AC: 691 AN: 4126

European-Finnish (FIN) AF: 0.361 AC: 3148 AN: 8718

Middle Eastern (MID) AF: 0.148 AC: 32 AN: 216

European-Non Finnish (NFE) AF: 0.242 AC: 13505 AN: 55694

Other (OTH) AF: 0.209 AC: 371 AN: 1774

Alfa AF: 0.200 Hom.: 391

Bravo AF: 0.176

Asia WGS AF: 0.156 AC: 540 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.94
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9333238; hg19: chr10-15573366;